Effects of metformin and statins on outcomes in men with castration-resistant metastatic prostate cancer: Secondary analysis of COU-AA-301 and COU-AA-302.

The associations of metformin and statins with overall survival (OS) and prostate specific antigen response rate (PSA-RR) in trials in metastatic castration-resistant prostate cancer remain unclear.

To determine whether metformin or statins ± abiraterone acetate plus prednisone/prednisolone (AAP) influence OS and PSA-RR.

COU-AA-301 and COU-AA-302 patients were stratified by metformin and statin use. Cox proportional hazards models were used to estimate hazards ratio (HR) stratified by concomitant medications, and a random effects model was used to pool HR. We compared PSA-RR using Chi χ2 test.

In COU-AA-301-AAP, metformin was associated with improved PSA-RR (41.1% versus 28.6%) but not prolonged OS. In COU-AA-301-placebo-P, there was no association between metformin and prolonged OS or PSA-RR. In COU-AA-302-AAP, metformin was associated with prolonged OS (adjHR 0.69, 95% CI 0.48-0.98) and improved PSA-RR (72.7% versus 60.0%). In COU-AA-302-P, metformin was associated with prolonged OS (adjHR 0.66, 95% CI 0.47-0.93). In pooled analysis, OS was prolonged among those treated with metformin (pooled HR 0.77, 95% CI 0.62-0.95).In COU-AA-301-AAP, statins were associated with an improved OS (adjHR 0.76, 95% CI 0.62-0.93), while there was no difference in COU-AA-301-P. There was no association with statins and OS in either COU-AA-302 groups. When pooling HR, OS was prolonged among those treated with statins (pooled HR 0.78, 95% CI 0.68-0.88).

Within the limitations of post-hoc sub-analyses, metformin and statins are associated with a prolonged OS and increased PSA-RR, particularly in combination with AAP.

European journal of cancer (Oxford, England : 1990). 2022 May 11 [Epub ahead of print]

Brooke E Wilson, Andrew J Armstrong, Johann de Bono, Cora N Sternberg, Charles J Ryan, Howard I Scher, Matthew R Smith, Dana Rathkopf, Christopher J Logothetis, Kim N Chi, Robert J Jones, Fred Saad, Peter De Porre, NamPhuong Tran, Peter Hu, Silke Gillessen, Joan Carles, Karim Fizazi, Anthony M Joshua

Princess Margaret Cancer Centre, Toronto, Canada; Faculty of Medicine, University of New South Wales, Kensington, Australia; Kinghorn Cancer Centre, St Vincents Hospital, Darlinghurst, Sydney, Australia., Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham NC, USA., The Institute of Cancer Research and Royal Marsden Hospital, London, UK., Englander Institute for Precision Medicine, Weill Cornell Medicine, New York-Presbyterian, New York, NY 10021, USA., Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA., Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA., Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, MA, 02114, USA., Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY USA., Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., BC Cancer, Vancouver, Canada., Institute of Cancer Sciences, University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, UK., Department of Urology, University of Montreal Hospital Center, Montreal, Quebec, Canada., Janssen R&D, Beerse, Belgium., Janssen R&D, Los Angeles, CA, USA., Janssen LLC. Raritan, New Jersey, USA., Institute of Oncology of Southern Switzerland, Bellinzona, Switzerland and Università Della Svizzera Italiana, Lugano, Switzerland and University of Manchester, UK., Vall D'Hebron Institute of Oncology, Vall D'Hebron University Hospital, Barcelona, Spain., Institut Gustave Roussy, University of Paris Saclay, Villejuif, France., Princess Margaret Cancer Centre, Toronto, Canada; Faculty of Medicine, University of New South Wales, Kensington, Australia; Kinghorn Cancer Centre, St Vincents Hospital, Darlinghurst, Sydney, Australia. Electronic address: .

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